Is RICTOR p.Ser1470Pro (c.4408T>C) pathogenic?

RICTOR p.Ser1470Pro (c.4408T>C) is classified Uncertain significance in RICTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.02%, sas).

How common is RICTOR p.Ser1470Pro (c.4408T>C) in the general population?

RICTOR p.Ser1470Pro (c.4408T>C) is ultra-rare (popmax 0.02%, sas) (gnomAD).

What do computational predictors say about RICTOR p.Ser1470Pro (c.4408T>C)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

RICTOR p.Ser1470Pro

c.4408T>C · rs763579152 · VCV3154233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 23 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% South Asian · 18/90,044 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00224% 35/1,559,290 alleles · ultra-rare exomes 34/1,407,054 · genomes 1/152,236 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.00494%	20,225
European (non-Finnish)	0.00124%	80,747

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RICTOR
Protein: p.Ser1470Pro
Coding: c.4408T>C
MANE Select: NM_152756
dbSNP: rs763579152
Type: single nucleotide variant
Location: chr5:38945716 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 16 PDB

Full RICTOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RICTOR p.Asn749= Benign ★★ same type
RICTOR p.Ile811= Benign ★★ same type
RICTOR p.His442Arg Likely pathogenic ★ ⚠ same type
RICTOR p.Ala1350Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala146Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala246Val Uncertain significance ★ ⚠ same type
RICTOR p.Ala472Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala91Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rictor-p-ser1470pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown